Physical and Logical

Physical

The first is the matter of how the physical folders and files are organized in your project directory. It's worth noting that, for the most part, this has little to do with how your project compiles and runs. With the exceptions of a few special folders (Resources, Plugins, etc), folders are just folders. Theoretically you could just lump every script, model and texture in one directory and not worry about it. That would be a bad idea.

Logical

The second is the logical layout of the program. This is the structure of classes and namespaces that you use. I'm not talking about the project file structure (auto-created by MonoDevelop or Visual Studio), but rather the logical structure of the game (where is player information stored? High scores? Level information? Enemy definitions, etc.).

Both of these structures are important, and getting them muddled can cause a great deal of confusion when a project becomes complex. Hopefully this will help anyone reading it to think about how they want to handle these issues.